Article Outline:

• Why do we need to gain?
• What is KPV? 
• Caloric Suplus Strategy 
• Caloric Surplus GI Distress 
• KPV Mechanism
• GI-Based Weight Gain Protocols

Anyone who says that gaining weight is easy has probably never attempted to do so. If you are looking to gain weight and are willing to do what is necessary to gain weight, you will need to address the collateral damage in your gut and to your immune system first. 

This article will address how to manage the side effects of gaining weight with KPV. KPV is an anti-inflammatory and antimicrobial peptide with strong preclinical support and growing evidence to support its role in the gastrointestinal tract and inflammatory response to eating and training. 

I have worked with college football for over 15 years. A large part of my job was helping offensive and defensive linemen gain weight. Most college football programs have to take chances on athletes who have the right frame but are undersized. That comes at a hidden cost. Increasing body mass by 25-50% in a couple of years is incredibly hard on the body, more specifically the digestive and the immune system. 

The single most important element of gaining weight is being in a caloric surplus. I start with a simple equation: bodyweight multiplied by 18-20. For example, if an athlete weighs 250lbs coming in, that would be 4500–5000 calories daily. We want a 500-1000 caloric surplus. That surplus represents the potential weight gain we are looking for. That is the first aspect to address with gut and inflammation. 

Hughes (2021) discussed how higher caloric intake (regardless of macronutrient composition) is positively correlated with serum zonulin levels and altered gut microbiota, including lower diversity and shifts in Firmicutes/Bacteroidetes. Athletes burn a lot of calories, and being in a surplus to offset that expenditure to gain weight can significantly impact gut bacteria diversity and gut permeability.  

Exercise alone has a profound effect on gut function. Hałasa (2019) found that professional athletes had significantly higher stool zonulin levels and intestinal permeability compared to amateurs and non-athletes (55 % vs. 22 % vs. 0 %), measured via lactulose/mannitol testing. Exercise combined with high-calorie diets can have a significant impact on gut function. Permeability is a real problem because it compounds autoimmunity. The surplus of calories causes compromised immune function at an even higher level when there are gut permeability issues. 

In terms of macros, 1gram per pound of goal weight. A goal weight of 300 pounds would be 300 grams or 1200 calories of protein daily. Carbohydrates are the most important macronutrient for athletes. Energy to train and energy to recover a foundational for adding lean muscle mass. Adding lean muscle mass is a costly activity. We need to have the requisite carbohydrates to perform tasks for lifting, running, and practicing. We also need to have an abundance of carbohydrates to refill glycogen stores following those activities, to perform again within a 12 to 24-hour period, as well as build muscle. A good target for carbohydrates is 2-3 grams per pound of current body weight. A 250lb athlete should be 500-750 grams or 2000 to 3000 calories daily. 

A myopic focus on protein and carbohydrates comes at a significant cost. Hughes (2021) found that maldigestion or incomplete absorption of proteins/carbs can increase substrate available for distal fermentation, potentially stressing the gut barrier, especially in calorie-intensive regimens. What we often lose sight of when eating such extreme amounts of food is that the quantity and frequency of eating are daunting for the athlete. Athletes chronically underchew food, leading to a greater challenge to their digestive system. The bolus of food is extremely monotonous and burdensome to do daily. The solution is to take in more broken-down (shakes/smoothies/broken down) foods, which can lead to other issues with blood sugar and insulin regulation. 

Yao (2015) found that excess protein (especially low-fiber, meat-heavy) leads to harmful fermentation metabolites and inflammation. Morh (2020) found that whey and animal proteins digest earlier; plant/poor‑quality proteins ferment distally, promoting dysbiosis. Lowering fiber and increasing supplemental forms of protein are critical strategies we have to utilize in order to gain weight. However, this creates a crossroads between efficacy and effectiveness: knowing the cost from a digestive standpoint and combining with the necessity to gain weight for performance, makes decisions very tough as a coach. This is where KPV comes in. 

Being proactive with managing gut stress is mission-critical with athletes who need to gain weight. The combined effect of training and being in an aggressive surplus demands your attention toward the side effects of GI distress. 

Being aware of symptoms such as bloating and gas, indigestion and heartburn, nausea, abdominal pain and cramping, diarrhea or constipation, and finally acne or skin disorders is paramount for success. These symptoms are all byproducts of GI distress from being in a caloric surplus. We want to limit symptoms by being proactive with food quality and supplementation. 

At the top of the list, quality matters. When in doubt, focus on animal-based protein and single-ingredient carbohydrate sources. Animal proteins should come from pasture-raised, wild-caught, and grass-fed/grass-finished. Carbohydrates should be organic and minimally processed. We simply have less latitude with processed or low-quality foods when we are at a surplus with the intent of adding lean muscle mass. Low quality amplifies side effects. 

All that is still not going to be enough; this is where KPV comes in. KPV is an anti‑inflammatory and antimicrobial peptide. KPV has shown benefits for gut barrier integrity and microbiome balance in colitis models and anecdotal use cases such as SIBO, IBS, and MCAS (Zhao, 2022). We can get more from our macronutrients and their conversion into direct performance during training sessions, as well as recovery from utilizing KPV. 

KPV is an immune-modulating agent. Dalmasso (2008) stated KPV penetrates cells and interferes with nuclear inflammatory signaling—such as NF‑κB and MAPK pathways—reducing cytokines like TNF‑α and IL‑6. Luger (2007) demonstrated that KPV has an impact on immune function through alpha‑melanocyte-stimulating hormone (α‑MSH), responsible for its potent anti‑inflammatory and immunomodulatory effects. The stress incurred from training is lessened with the utilization of KPV. 

There is promising evidence based on KPV’s immune attenuating mechanisms on downstream positive effects on tendonopathy. The fact that KPV has an impact on reducing immune response leads to better functioning of not just the gut, but the musculoskeletal system we are stressing daily to change lean body mass. 

The protocol: 

• Caloric Intake: 
  • 500-1000 daily surplus 
  • Multiple bodyweight by 18-20
• Macronutrients:
  • Protein: 1gram per pound of goal bodyweight 
    • 80-90% from pasture-raised, wild-caught, grass-fed/grass-finished animal sources
    • 10-20% from grass-fed/grass-finished whey or beef isolate, or pea/hemp/rice protein blend 
  • Carbohydrates: 2-3grams per pound of current bodyweight 
    • 100% from single-ingredient organic sources 
  • Fat: Remaining Balance of Calories broken evenly into saturated, monounsaturated, and polyunsaturated 
• Supplementation: 
  • 2 KPV LPT taken daily in the morning on an empty stomach
    • Restore gut and lower inflammation from caloric surplus 
• Optional Supplements:
  • 2 TetraCur LPT taken daily in the morning on an empty stomach
    • Reduce the inflammatory response to caloric surplus 
  • 2 ModuCare ES taken daily in the morning on an empty stomach
    • Reduce the immune response to training 
  • 1 MAX 12 Probiotic taken daily in the morning after breakfast
    • Repopulate gut bacteria with high quantities of proteins and carbohydrates. 

The combined stress of being in a surplus and training with high intensity creates a fundamental need to address gut function in athletes. It is not enough to simply eat clean. The stress on the gut from that surplus, along with training stress, is too much for the system to bear without supplemental help. KPV will be a foundational supplement for anyone who needs to gain weight in order to limit side effects from caloric surplus. 

References

Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, Yan Y, Sitaraman S, Merlin D. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008;134(1):166-178. doi:10.1053/j.gastro.2007.10.026

Xiao B, Xu Z, Viennois E, et al. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Mol Ther. 2017;25(7):1628-1640. doi:10.1016/j.ymthe.2016.11.020

https://peptide-hub.com/pages/exploring-the-anti-inflammatory-and-healing-potential-of-kpv-peptide?utm_source=chatgpt.com

Luger TA, Brzoska T. alpha-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs. Ann Rheum Dis. 2007;66 Suppl 3(Suppl 3):iii52-iii55. doi:10.1136/ard.2007.079780

Hałasa M, Maciejewska D, Ryterska K, Baśkiewicz-Hałasa M, Safranow K, Stachowska E. Assessing the Association of Elevated Zonulin Concentration in Stool with Increased Intestinal Permeability in Active Professional Athletes. Medicina (Kaunas). 2019;55(10):710. Published 2019 Oct 21. doi:10.3390/medicina55100710

Hughes RL, Holscher HD. Fueling Gut Microbes: A Review of the Interaction between Diet, Exercise, and the Gut Microbiota in Athletes. Adv Nutr. 2021;12(6):2190-2215. doi:10.1093/advances/nmab077

Hughes RL, Holscher HD. Fueling Gut Microbes: A Review of the Interaction between Diet, Exercise, and the Gut Microbiota in Athletes. Adv Nutr. 2021;12(6):2190-2215. doi:10.1093/advances/nmab077. 

​​Mohr, A.E., Jäger, R., Carpenter, K.C. et al. The athletic gut microbiota. J Int Soc Sports Nutr 17, 24 (2020). https://doi.org/10.1186/s12970-020-00353-w 

2015. K. Yao, J. G. Muir & P. R. Gibson. Review article: insights into colonic protein fermentation, its modulation and potential health implications. 2015. Aliment Pharmacol Ther 2016; 43: 181–196. doi:10.1111/apt.13456 

Zhao Y, Xue P, Lin G, Tong M, Yang J, Zhang Y, Ran K, Zhuge D, Yao Q, Xu H. A KPV-binding double-network hydrogel restores gut mucosal barrier in an inflamed colon. Acta Biomater. 2022 Apr 15;143:233-252. doi: 10.1016/j.actbio.2022.02.039. Epub 2022 Mar 1. PMID: 35245681.